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Potential Endocrine Disrupting Effects of Phthalates in In Vitro and In Vivo Models  

Nguyen, Tien-Thanh (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Jung, Eui-Man (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Yang, Hyun (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Hyun, Sang-Hwan (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Choi, Kyung-Chul (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Jeung, Eui-Bae (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
Publication Information
Journal of Embryo Transfer / v.25, no.4, 2010 , pp. 207-213 More about this Journal
Abstract
Thousands of new chemicals have been introduced to environment during last decades. Many of them and common consumer products have been shown to be the endocrine disrupting chemicals. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. The prevalence of these modem chemicals have a remarkable increase. Approximately 3.5 million tons of the main phthalate, di-(2-ethylhexyl) phthalate (DEHP), are produced annually worldwide and indeed, DEHP is considered a ubiquitous environmental contaminant. It has been demonstrated that high doses of phthalate can adversely affect adult and developing animals. In this review, we critically discuss the conclusions of recently original research papers and provide an overview of studies on reproductive disrupting effects of phthalates. In addition, we review the reproductive toxicity data of phthalates in some in vitro research and in both male and female reproductive systems in experimental and domestic animals. Finally, we point out some critical issues that should be addressed in order to clarify the implication of phthalates for human reproduction.
Keywords
phthalates; endocrine disruption; reproductive system; in vivo; in vitro;
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1 Grande SW, Andrade AJ, Talsness CE, Grote K, Golombicwski A, Sterner-Kock A and Chahoud I. 2007. A dose. response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult female offspring rats. Toxicology 229:114-122.   DOI
2 Wams TJ. 1987. Diethylhexylphthalate as an environmental contaminant-A review. Sci. Total Environ. 66:1-16.   DOI
3 Kavlock R, Boekelheide K, Chapin R, Cunningham M, Faustman E, Foster P, Golub M, Henderson R, Hinberg I, Little R, Seed J, Shea K, Tabacova S, Tyl R, Williams P and Zacharewski T. 2002. NTP center for the evaluation of risks to human reproduction: Phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate. Reprod. Toxicol. 16:529-653.   DOI   ScienceOn
4 Grande SW, Andrade AJ, Talsness CE, Grote K and Chahoud I. 2006. A dose-response study following in utero and lactational exposure to di(2-ethylhexyl)phthalate: Effects on female rat reproductive development. Toxicol. Sci. 91:247-254.   DOI   ScienceOn
5 Arcadi FA, Costa C, Imperatore C, Marchese A, Rapisarda A, Salemi M, Trimarchi GR and Costa G. 1998. Oral toxicity of bis(2-ethylhexyl) phthalate during pregnancy and suckling in the Long-Evans rat. Food Chem. Toxicol. 36:963-970.   DOI   ScienceOn
6 Vo TT, Jung EM, Dang VH, Jung K, Baek J, Choi KC and Jeung EB. 2009. Differential effects of flutamide and di-(2-ethylhexyl) phthalate on male reproductive organs in a rat model. J. Reprod. Dev. 55:400-411.   DOI   ScienceOn
7 Wormuth M, Scheringer M, Vollenweider M and Hungerbuhler K. 2006. What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal. 26:803-824.   DOI   ScienceOn
8 Lamb JCT, Chapin RE, Teague J, Lawton AD and Reel JR. 1987. Reproductive effects of four phthalic acid esters in the mouse. Toxicol. Appl. Pharmacol. 88:255-269.   DOI   ScienceOn
9 Liu K, Lehmann KP, Sar M, Young SS and Gaido KW. 2005. Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biol. Reprod. 73:180-192.   DOI   ScienceOn
10 Ren L, Marquardt MA and Lech JJ. 1997. Estrogenic effects of nonylphenol on pS2, ER and MUC1 gene expression in human breast cancer cells-MCF-7. Chem. Biol. Interact. 104:55-64.   DOI   ScienceOn
11 Anas MK, Suzuki C, Yoshioka K and Iwamura S. 2003. Effect of mono-(2-ethylhexyl) phthalate on bovine oocyte maturation in vitro. Reprod. Toxicol. 17:305-310.   DOI   ScienceOn
12 Bosnir J, Puntaric D, Skes I, Klaric M, Simic S and Zoric I. 2003. Migration of phthalates from plastic products to model solutions. Coll. Antropol. 27 Suppl. 1:23-30.
13 Calafat AM, Brock JW, Silva MJ, Gray LE Jr, Reidy JA, Barr DB and Needham LL. 2006. Urinary and anmiotic fluid levels of phthalate monoesters in rats after the oral administration of di(2-ethylhexyl) phthalate and di-n-butyl phthalate. Toxicology 217:22-30.   DOI   ScienceOn
14 Choi KC and Jeung EB. 2003. The biomarker and endocrine disruptors in mammals. J. Reprod. Dev. 49:337-345.   DOI   ScienceOn
15 Shirota M, Saito Y, Imai K, Horiuchi S, Yoshimura S, Sato M, Nagao T, Ono H and Katoh M. 2005. Influence of di-(2-ethylhexyl)phthalate on fetal testicular development by oral administration to pregnant rats. J. Toxicol. Sci. 30:175-194.   DOI   ScienceOn
16 Andrade AJ, Grande SW, Talsness CE, Gericke C, Grote K, Golombiewski A, Sterner-Kock A and Chahoud I. 2006a. A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats. Toxicology 228:85-97.   DOI   ScienceOn
17 Andrade AJ, Grande SW, Talsness CE, Grote K, Golombiewski A, Sterner-Kock A and Chahoud I. 2006b. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Effects on androgenic status, developmental landmarks and testicular histology in male offspring rats. Toxicology 225:64-74.   DOI   ScienceOn
18 Wieslander G, Norback D, Nordstrom K, Walinder R and Venge P. 1999. Nasal and ocular symptoms, tear film stability and biomarkers in nasal lavage, in relation to building-dampness and building design in hospitals. Int. Arch. Occup. Environ. Health 72:451-461.   DOI   ScienceOn
19 Wittassek M and Angerer J. 2008. Phthalates: Metabolism and exposure. Int. J. Androl. 31:131-138.   DOI   ScienceOn
20 Wittassek M, Heger W, Koch HM, Becker K, Angerer J and Kolossa-Gehring M. 2007. Daily intake of di(2-ethylhexyl) phthalate (DEHP) by German children - A comparison of two estimation models based on urinary DEHP metabolite levels. Int. J. Hyg. Environ. Health 210:35-42.   DOI   ScienceOn
21 Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N and Serrano FO. 1995. The E-SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ. Health. Perspect. 103 Suppl 7:113-122.   DOI
22 Swan SH 2008. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ. Res. 108:177-184.   DOI   ScienceOn
23 Takehisa H, Naoko E, Masahiko S, Katsuhide T, Moriyuki O, Keizoh S, Mutsuko T, Kenji K, Shin'ichiro N and Toshio O. 2005. Release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing used for intravenous administration and the plasticized PVC membrane. Int. J. Pharm. 297:30-37.   DOI   ScienceOn
24 Reinsberg J, Wegener-Toper P, van der Ven K, van der Ven H and Klingmueller D. 2009. Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells. Toxicol. Appl. Pharmacol. 239:116-123.   DOI   ScienceOn
25 Nagao T, Ohta R, Marumo H, Shindo T, Yoshimura S and Ono H. 2000. Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: A two-generation reproductive study. Reprod. Toxicol. 14:513-532.   DOI   ScienceOn
26 Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ and Gray LE Jr. 2000. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci. 58:339-349.   DOI
27 Parveen M, Inoue A, Ise R, Tanji M and Kiyama R. 2008. Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (EstrArray). Environ. Toxicol. Chem. 27:1416-1425.   DOI   ScienceOn
28 Rhind SM, Kyle CE, Telfer G, Duff EI and Smith A. 2005. Alkyl phenols and diethylhexyl phthalate in tissues of sheep grazing pastures fertilized with sewage sludge or inorganic fertilizer. Environ. Health Perspect. 113:447-453.   DOI   ScienceOn
29 Lehmann KP, Phillips S, Sar M, Foster PM and Gaido KW 2004. Dose-dependent alterations in gene expression and testosterone synthesis in the fetal testes of male rats exposed to di (n-butyl) phthalate. Toxicol. Sci. 81:60-68.   DOI
30 Latini G, Verrotti A and De Felice C. 2004. DI-2-ethylhexyl phthalate and endocrine disruption: A review. Curr. Drug Targets Immune Endocr. Metabol. Disord. 4:37-40.   DOI   ScienceOn
31 Lin H, Lian QQ, Hu GX, Jin Y, Zhang Y, Hardy DO, Chen GR, Lu ZQ, Sottas CM, Hardy MP and Ge RS. 2009. In utero and lactational exposures to diethylhexyl-phthalate affect two populations of Leydig cells in male Long-Evans rats. Biol. Reprod. 80:882-888.   DOI   ScienceOn
32 Moore NP. 2000. The oestrogenic potential of the phthalate esters. Reprod. Toxicol. 14:183-192.   DOI   ScienceOn
33 Moore RW, Rudy TA, Lin TM, Ko K and Peterson RE. 2001. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer di(2-ethylhexyl) phthalate. Environ. Health Perspect. 109:229-237.   DOI   ScienceOn
34 Latini G, Del Vecchio A, Massaro M, Verrotti A and De Felice C. 2006a. In utero exposure to phthalates and fetal development. Curr. Med. Chem. 13:2527-2534.   DOI   ScienceOn
35 Mylchreest E, Sar M, Wallace DG and Foster PM. 2002. Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reprod. Toxicol. 16:19-28.   DOI   ScienceOn
36 Koch HM, Drexler H and Angerer J. 2003. An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. Int. J. Hyg. Environ. Health 206:77-83.   DOI   ScienceOn
37 Kumar R, Wieben E and Beecher SJ. 1989. The molecular cloning of the complementary deoxyribonucleic acid for bovine vitamin D-dependent calcium-binding protein: Structure of the full-length protein and evidence for homologies with other calcium-binding proteins of the troponin-C superfamily of proteins. Mol. Endocrinol. 3:427-432.   DOI   ScienceOn
38 Latini G, Del Vecchio A, Massaro M, Verrotti A and De Felice C. 2006b. Phthalate exposure and male infertility. Toxicology 226:90-98.   DOI
39 Hirosawa N, Yano K, Suzuki Y and Sakamoto Y. 2006. Endocrine disrupting effect of di-(2-ethylhexyl)phthalate on female rats and proteome analyses of their pituitaries. Proteomics 6:958-971.   DOI   ScienceOn
40 Heppell SA, Denslow ND, Folmar LC and Sullivan CV 1995. Universal assay of vitellogenin as a biomarker for environmental estrogens. Environ. Health Perspect. 103 Suppl 7:9-15.   DOI
41 Hong EJ, Ji YK, Choi KC, Manabe N and Jeung EB. 2005. Conflict of estrogenic activity by various phthalates between in vitro and in vivo models related to the expression of Calbindin-D9k. J. Reprod. Dev. 51:253-263.   DOI   ScienceOn
42 Jobling S, Reynolds T, White R, Parker MG and Sumpter JP. 1995. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ. Health Perspect. 103:582-587.   DOI   ScienceOn
43 Gray LE Jr, Wolf C, Lambright C, Mann P, Price M, Cooper RL and Ostby J. 1999. Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol. Ind. Health 15:94-118.
44 Koch HM, Bolt HM, Preuss R and Angerer J. 2005. New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP. Arch. Toxicol. 79:367-376.   DOI   ScienceOn
45 Gray LE Jr, Laskey J and Ostby J. 2006. Chronic di-n-butyl phthalate exposure in rats reduces fertility and alters ovarian function during pregnancy in female Long Evans hooded rats. Toxicol. Sci. 93:189-195.   DOI   ScienceOn
46 Gray LE Jr, Ostby J, Furr J, Price M, Veeramachaneni DN and Parks L. 2000. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol. Sci. 58:350-365.   DOI
47 Dang VH, Choi KC, Hyun SH and Jeung EB 2007. Analysis of gene expression profiles in the offspring of rats following maternal exposure to xenoestrogens. Reprod. Toxicol. 23:42-54.   DOI   ScienceOn
48 Harris CA, Henttu P, Parker MG and Sumpter JP. 1997. The estrogenic activity of phthalate esters in vitro. Environ. Health Perspect. 105:802-811.   DOI   ScienceOn
49 Harrison PT, Holmes P and Humfrey CD. 1997. Reproductive health in humans and wildlife: Are adverse trends associated with environmental chemical exposure? Sci. Total Environ. 205:97-106.   DOI
50 Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A and Hass U. 2009. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ. Health Perspect. 117:1839-1846.
51 Davis BJ, Maronpot RR and Heindel JJ. 1994. Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats. Toxicol. Appl. Pharmacol. 128:216-223.   DOI   ScienceOn
52 Fabjan E, Hulzebos E, Mennes W and Piersma AH. 2006. A category approach for reproductive effects of phthalates. Crit. Rev. Toxicol. 36:695-726.   DOI   ScienceOn
53 Bornehag CG, Sundell J, Weschler CJ, Sigsgaard T, Lundgren B, Hasselgren M and Hagerhed-Engman L. 2004. The association between asthma and allergic symptoms in children and phthalates in house dust: A nested case-control study. Environ. Health Perspect. 112:1393-1397.   DOI   ScienceOn
54 Foster PM, Mylchreest E, Gaido KW and Sar M. 2001. Effects of phthalate esters on the developing reproductive tract of male rats. Hum. Reprod. Update 7:231-235.   DOI   ScienceOn
55 Asai D, Tahara Y, Nakai M, Yakabe Y, Takatsuki M, Nose T, Shinmyozu T and Shimohigashi Y. 2000. Structural essentials of xenoestrogen dialkyl phthalates to bind to the estrogen receptors. Toxicol. Lett. 118:1-8.   DOI
56 Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, Lucier GW, Jackson RJ and Brock JW. 2000. Levels of seven urinary phthalate metabolites in a human reference population. Environ. Health Perspect. 108:979-982.